To our knowledge, this is the first report of a study focusing on the efficacy of IUI program in women with endometrioma-associated subfertility using a PSM technique. Compared with unexplained subfertile women in the matched group, the odds of per-cycle PR in subfertile women with endometriomas were 0.47 (95% CI, 0.21-1.03) and odds of CPRs were 0.54 (95% CI, 0.26-1.15). However, none of the estimations were statistically significant. We found that patients with endometriomas were nearly twice as likely to converse to IVF treatment compared with those without the disease. Subgroup analyses based on with/without prior surgery for endometrioma did not impact the outcomes. Although for women with endometrioma, stimulation cycles seemed to result in a slightly higher PR per cycle than that in natural cycles (11.9% vs. 6.7%, P=0.404), the difference was not significant.
Comparison To Other Studies
Similar findings have been reported for moderate-to-severe endometriosis. van der Houwen et al.  suggested that IUI was a valuable infertility management in women with more severe endometriosis, namely moderate-to-severe endometriosis. The CPRs of 28% in patients with Stage III and Stage IV endometriosis after six subsequent IUI cycles were reported. In the current study, the CPRs in women with endometrioma were lower than that in women with unexplained infertility (14.3% versus 28.9%; P=0.108), but the difference was not significant. It has been noted that majority couples in the study received no more than 4 cycles of IUI treatment. Although it reflects daily practice, we cannot exclude the possibility that exposure to more cycles of IUI could have led to a significant difference in CPR in both groups.
The optimum cycles of IUI attempts has been a pragmatic and challenge question when counseling couples. One previous publishing, concluded that IUI for treatment of unexplained infertility should be limited to a maximum of three cycles . In the current study, a significant more women with endometrioma resorted to IVF treatment compared with those without the disease. We also found that for women with endometrioma, starting from the third cycle onward, additional attempts have only rarely increased fecundability. Although these could be attributed by chance, the results also suggested that women with subfertility and endometrioma may be reassured by more active and aggressive reproductive technology. we assume this information will be helpful in the counselling process. Some selected patients may be better served by IVF procedure if they fail to conceive after two cycles of IUI. Further data on this issue are needed.
It is still debatable whether IUI with stimulation is superior to unstimulated IUI. A pragmatic randomised controlled trial failed to show any advantage of superovulation over unstimulated IUI in couples with unexplained infertility . While the Cochrane view supported clomifene citrate administration and suggested it had a beneficial effect in unexplained infertility . In a recent study, an increased cumulative pregnancy rate has been shown in patients receiving IUI with stimulation up to six cycles compared to three times IUI without stimulation followed by up to three times IUI with stimulation, which endorsed the cochrane view . In our study, when compared to IUI without stimulation, ovarian stimulation seemed to result in a slightly higher PR per cycle in women with subfertility and endometrioma (11.9% vs. 6.7%, P=.404). Differences in the two protocols that are close to statistical significance, increasing the sample size of patients may reveal meaningful role of ovarian stimulation in IUI program. The rationale for ovarian stimulation in women with endometrioma has been to correct potential disorders of endocrine and ovulation, including luteinized unruptured follicle syndrome, abnormal follicular growth, and premature LH surges .
However, ovarian stimulation may cause some concerns among patients. Impact of ovarian stimulation on the progression of endometriosis or its recurrence was recently summarized in a systematic review . According to their report, impact of ovarian stimulation on ovarian endometrioma, if present, is clinically unremarkable. In the present study with multiple simulated IUI cycles, no bleeding, infection and other related complications was reported. All these results can be used to reassure patients.
Strengths And Limitations
One of the major strengths of this study was the use of PSM analysis to achieve matched groups. Evaluating and comparing treatment strategies for subfertile women with endometrioma alone is limited by heterogeneous practices between clinicians and centers. We specifically focused on this point by matching multiple clinical covariates in patients performing IUI. Secondly, at the present study, we compared the effectiveness of IUI on women with endometrioma alone versus women with unexplained subfertility. The assessment was specifically confined to the impact of ovarian endometrioma alone. Definition of the “true” unexplained infertility is still controversial. Some women in the unexplained subfertility group might have undetected minimal or mild endometriosis. However, that inclusion of the control group means that our results reflect the true contributory effect of the endometrioma alone with.
This study had some limitations deserve to be underlined. The relatively small sample size of the present study, may be underpowered to detect a significant difference in reproductive outcomes. Hence the results should be interpreted with caution. Our choice of clinical protocols for the management of subfertile women with endometrioma reflects current practice in our center and the rest of the China, but the results might not be generalizable to other populations and alternative national funding strategy. The inclusion of women with endometrioma could be diagnosed by laparoscopy or imaging detection might have introduced an factor of heterogeneity. Not reliably imaging peritoneal implants of endometriosis, however, transvaginal ultrasound have shown to have good accuracy for ovarian endometioma (95.1%~96% specificity and 93~94.7% sensitivity) [24, 25], which is also recommended by ARSM . There were few pregnancies within each subgroup (endometrioma diagnosed with/without prior surgery), sensitivity analyses indicate similar IUI treatment effects. We did not find any RCTs comparing reproductive outcomes after endometrioma cystectomy versus no treatment in women with endometrioma and addressing if IUI procedure is more successful post cystectomy compared to untreated. Future research should focus on more uniform control group and addressing the issues.